Since HMG-CoA reductase is a major site of control of cholesterol biosynthesis under most physiological conditions, it is proposed to investigate the mechanism of the effect of a variety of physiological states on HMG-CoA reductase activity, e.g., fasting, cholesterol feeding, supplementation with hormones, and interruption of the enterohepatic circulation of bile. The synthesis and degradation of the enzyme protein as well as possible allosteric affects will be studied in liver and intestinal mucosal cells by means of immunochemical techniques, which will enable the enzyme protein to be extracted from crude cell homogenates relatively easily. Another line of research is focused on studying the physical chemical characteristics of the enzyme especially changes in activity that result from alterations in the interactions between the lipid associated with the enzyme and enzyme protein. Various physical techniques are being used to study these changes, especially circular dichroism spectra in the near and far ultraviolet spectrum.